Alignments of endocrine, anthropometric, and metabolic parameters in type 2 diabetes after intervention with an Okinawa-based Nordic diet

  • Bodil Ohlsson
  • Gassan Darwiche
  • Bodil Roth
  • Peter Höglund
Keywords: adipokines, incretins, gut hormones, Okinawan-based Nordic diet, metabolic control


Background: An Okinawa-based Nordic diet with moderately low carbohydrate content and high fat and protein content has been shown to improve anthropometry and metabolism in type 2 diabetes.

Objective: The objectives of this study were to measure plasma or serum levels of hormones regulating energy metabolism and metabolic control, that is, cholecystokinin (CCK), Cortisol, C-peptide, ghrelin, glucagon, glucagon- like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, leptin, plasminogen activator inhibitor-1 (PAI-1), polypeptide YY (PYY), resistin, and visfatin after this diet intervention, and to determine partial correlations between hormonal levels and anthropometric and metabolic responses.

Design: A total of 30 patients (17 women) with type 2 diabetes, mean age 57.5 ± 8.2 years, and body mass index (BMI) 29.9 ± 4.1 kg/m2 were served the diet for 12 weeks. Fasting hormones were measured by Luminex and enzyme–linked immunosorbent assay (ELISA) before study start and after 12 and 28 weeks, along with anthropometric and metabolic parameters.

Result: The levels of CCK (P = 0.005), cortisol (P = 0.015), C-peptide (P = 0.022), glucagon (P = 0.003), GLP-1 (P = 0.013), GIP (P < 0.001), insulin (P = 0.004), leptin (P < 0.001), and PYY (P < 0.001) were lowered after dietary intervention. These reduced levels only remained for PYY at week 28 (P = 0.002), when also ghrelin (P = 0.012) and visfatin (P = 0.021) levels were reduced. Changes of glucose values correlated with changed levels of C-peptide and PYY (P < 0.001), insulin (P = 0.002), and PAI-1 (P = 0.009); changes of triglyceride values with changed levels of C-peptide, insulin, and PYY (P < 0.001) and PAI-1 (P = 0.005); changes of insulin resistance with changes of leptin levels (P = 0.003); and changes of BMI values with changed levels of C-peptide, insulin, and leptin (P < 0.001).

Conclusions: Okinawa-based Nordic diet in type 2 diabetes has significant impact on the endocrine profile, which correlates with anthropometric and metabolic improvements.


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  1. Willcox DC, Scapagnini G, Willcox BJ. Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet. Mech Ageing Dev 2014; 136–137: 148–62.

  2. O’Keefe JH, Gheewala NM, O’Keefe JO. Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health. J Am Coll Cardiol 2008; 51: 249–55.

  3. Darwiche G, Höglund P, Roth B, Larsson E, Sjöberg T, Wohlfart B, et al. An Okinawan-based Nordic diet improves anthropometry, metabolic control, and quality of life in Scandinavian patients with type 2 diabetes: a pilot trial. Food Nutr Res 2016; 60: 32594.

  4. Ohlsson B, Höglund P, Roth B, Darwiche G. Modification of a traditional breakfast leads to increased satiety along with attenuated plasma increments of glucose, C-peptide, insulin, and GIP in human. Nutr Res 2016; 36: 359–68.

  5. Yoder SM, Yang Q, Kindel TL, Tso P. Differential responses of the incretin hormones GIP and GLP-1 to increasing doses of dietary carbohydrate but not dietary protein in lean rats. Am J Physiol Gastrointest Liver Physiol 2010; 299: G476–85.

  6. Yoder SM, Yang Q, Kindel TL, Tso P. Stimulation of incretin secretion by dietary lipid: is it dose dependent? Am J Physiol Gastrointest Liver Physiol 2009; 297: G299–305.

  7. Asmar M, Simonsen L, Madsbad S, Stallknecht B, Holst JJ, Bülow J. Glucose-dependent insulinotropic polypeptide may enhance fatty acid re-esterification in subcutaneous abdominal adipose tissue in lean humans. Diabetes 2010; 59: 2160–3.

  8. Holst JJ, Vilsbøll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol 2009; 297: 127–36.

  9. Gutierrez-Aguilar R, Woods SC. Nutrition and L and K-enteroendocrine cells. Curr Opin Endocrinol Diabetes Obes 2011; 18: 35–41.

  10. Overduin J, Gibbs J, Cummings DE, Reeve JR Jr. CCK-58 elicits both satiety and satiation in rats while CCK-8 elicits only satiation. Peptides 2014; 54: 71–80.

  11. Cooper JA. Factors affecting circulating levels of peptide YY in humans: a comprehensive review. Nutr Res Rev 2014; 27: 186–97.

  12. Persaud SJ, Bewick GA. Peptide YY: more than just an appetite regulator. Diabetologia 2014; 57: 1762–9.

  13. Chu S, Schubert ML. Gastric secretion. Curr Opin 2013; 29: 636–41.

  14. AL-Suhaimi EA, Shehzad A. Leptin, resistin and visfatIn: the missing link between endocrine metabolic disorders and immunity. Eur J Med Res 2013; 18: 12.

  15. Tilg H, Moschen AR. Role of adiponectin and PBEF/visfatin as regulator f inflammation: involvement in obesity-associated diseases. Clin Sci 2008; 114: 275–88.

  16. Nordt TK, Sawa H, Fujii S, Bode C, Sobel BE. Augmentation of arterial endothelial cell expression of the plasminogen activator inhibitor typ-1 (PAI-1) gene by proinsulin and insulin in vivo. J Mol Cell Cardiol 1998; 30: 1535–43.

  17. Anagnostis P, Athyros VG, Tziomalos K, Karagiannis A, Mikhailidis DP. Clinical review: the pathogenetic role of cortisol in the metabolic syndrome: a hypothesis. J Clin Endocrinol Metab 2009; 94: 2692–701.

  18. Nordic Nutrition Recommendations 2012. Available from: Cited 3 April 2017.

  19. World Health Organization. Global database on body mass index; 2015. Available from: Cited 3 April 2017.

  20. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults–The Evidence Report: National Institutes of Health. Obes Res 2008; 6(Suppl 2): 51S–209S.

  21. The Oxford Centre for Diabetes, Endocinology, and Metabolism, Diabetes Trials Unit. The University of Oxford. 2016. Cited 12 January 2016.

  22. Wing RR, Lang W, Wadden TA, Safford M, Knowler WC, Bertoni AG, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care 2011; 34: 1481–6.

  23. Højberg PV, Vilsbøll T, Zander M, Knop FK, Krarup T, Vølund A, et al. Four weeks of near-normalization of blood glucose has no effect on postprandial GLP-1 and GIP secretion, but augments pancreatic B-cell responsiveness to a meal in patients with Type 2 diabetes. Diabet Med 2008; 25: 1268–75.

  24. Smeets AJ, Westerterp-Plantenga MS. Acute effects on metabolism and appetite profile of one meal difference in the lower range of meal frequency. Br J Nutr 2008; 99: 1316–21.

  25. Smeets AJ, Soenen S, Luscombe-Marsh ND. Energy expenditure, satiety, and plasma ghrelin, glucagon-like peptide 1, and peptide tyrosine-tyrosine concentrations following a single high-protein lunch. J Nutr 2008; 138: 698–702.

  26. Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med 2011; 365: 1597–604.

  27. Delzenne N, Blundell J, Brouns F, Cunningham K, De Graaf K, Erkner A, et al. Gastrointestinal targets of appetite regulation in humans. Obes Rev 2010; 11: 234–50.

  28. Ohlsson B, Darwiche G, Roth B, Bengtsson M, Höglund P. High fiber, fat and protein contents lead to increased satiety, reduced sweet cravings, and decreased gastrointestinal symptoms, independently of anthropometric, hormonal, and metabolic factors. J Diabet Metabol 2017; 8: 3.

  29. Lean ME, Malkova D. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence? Int J Obes 2016; 40: 622–32.

  30. Adamsson V, Reumark A, Fredriksson IB, Hammarström E, Vessby B, Johansson G, et al. Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects: a randomized controlled trial (NORDIET). J Intern Med 2011; 269: 150–9.

  31. Heller RF. Hyperinsulinemic obesity and carbohydrate addiction: the missing link is the carbohydrate frequency factor. Med Hypotheses 1994; 42: 307–12.

  32. Yip RG, Wolfe MM. GIP biology and fat metabolism. Life Sci 2000; 66: 91–103.

  33. Peracchi M, Santangelo A, Conte D, Fraquelli M, Tagliabue R, Gebbia C, et al. The physical state of a meal affects hormone release and postprandial thermogenesis. Br J Nutr 2000; 83: 623–8.

  34. Shimotoyodome A, Fukuoka D, Suzuki J. Coingestion of acylglycerols differentially affects glucose-induced insulin secretion via glucose-dependent insulinotropic polypeptide in C57BL/6J mice. Endocrinology 2009; 150: 2118–26.

  35. de Faria AP, Modolo R, Fontana V, Moreno H. Adipokines: novel players in resistant hypertension. J Clin Hypertens 2014; 16: 754–59.

  36. Vinales KL, Schlögl M, Piaggi P, Hohenadel M, Graham A, Bonfiglio S et al. The consistency in macronutrient oxidation and the role for epinephrine in the response to fasting and overfeeding. J Clin Endocrinol Metab 2017; 102:279–89.

  37. Carlson O, Martin B, Stote KS, Golden E, Maudsley S, Najjar SS, et al. Impact of reduced meal frequency without caloric restriction on glucose regulation in healthy, normal-weight middle-aged men and women. Metabolism 2007; 56: 1729–34.

  38. Fallucca F, Fontana L, Fallucca S, Pianesi M. Gut microbiota and Ma-Pi 2 macrobiotic diet in the treatment of type 2 diabetes. World J Diabetes 2015; 6: 403–11.

  39. Bakhøj S, Flint A, Holst JJ, Tetens I. Tetens I. Lower glucose-dependent insulinotropic polypeptide (GIP) response but similar glucagon-like peptide 1 (GLP-1), glycaemic, and insulinaemic response to ancient wheat compared to modern wheat depends on processing. Eur J Clin Nutr 2003; 57: 1254–61.

  40. Tovar J, Nilsson A, Johansson M, Björck I. Combining functional features of whole-grain barley and legumes for dietary reduction of cardiometabolic risk: a randomised cross-over intervention in mature women. Br J Nutr 2014; 111: 706–14.

  41. Zhong Y, Nyman M, Fåk F. Modulation of gut microbiota in rats fed high-fat diets by processing whole-grain barley to barley malt. Mol Nutr Food Res 2015; 59: 2066–76.

  42. Johnsen NF, Frederiksen K, Christensen J, Skeie G, Lund E, Landberg R, et al. Whole-grain products and whole-grain types are associated with lower all-cause and cause-specific mortality in the Scandinavian HELGA cohort. Br J Nutr 2015; 23: 1–16.

  43. Williams PG. The benefits of breakfast cereal consumption: a systematic review of the evidence base. Adv Nutr 2014; 5: 636S–73S.

  44. Egeberg R, Frederiksen K, Olsen A, Johnsen NF, Loft S, Overvad K, et al. Intake of wholegrain products is associated with dietary, lifestyle, anthropometric and socio-economic factors in Denmark. Public Health Nutr 2009; 12: 1519–30.

  45. Hammersjö R, Roth B, Höglund P, Ohlsson B. Esophageal and gastrointestinal motility affects glucose homeostasis and plasma levels of incretin and leptin. Rev Diab Stud 2016; 13: 79–90.

  46. Drazen DL, Vahl TP, D’Alessio DA, Seeley RJ, Woods SC. Effects of a fixed meal pattern on ghrelin secretion: evidence for a learned response independent of nutrient status. Endocrinology 2006; 147: 23–30.

How to Cite
Ohlsson B, Darwiche G, Roth B, Höglund P. Alignments of endocrine, anthropometric, and metabolic parameters in type 2 diabetes after intervention with an Okinawa-based Nordic diet. Food & Nutrition Research [Internet]. 14Mar.2018 [cited 20Sep.2018];62. Available from:
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